3^rd International Conference on Genomics & Pharmacogenomics September 21-23, 2015 San Antonio, USA

Biography:

Dr. Campbell completed his PhD from the University of Arizona and postdoctoral studies from the University of Wisconsin Madison. This work has resulted in and more than 14 publications since 2009. He began as an Assistant Professor at UT-Dallas in the Department of biological sciences in August.

Abstract:

Targeted control of mRNAs by proteins requires an easily programmable scaffold. PUF domain proteins provide an attractive platform for that purpose. Like TALENs and zinc fingers, which target DNA via reiterated modules, PUF proteins possess simple repeated domains. These target RNA rather than DNA, and so provide an opportunity to control translation, decay and processing of mRNAs. PUF proteins bind to single-stranded RNA using eight repeated modules, each of which contributes three amino acids that contact an RNA base. Here, we identify the specificities of natural and designed combinations of these three amino acids. Our strategy to assay RNA-protein interactions (SEQRS) integrates in vitro selection, high-throughput sequencing of RNA, and SSLs (sequence specificity landscapes) [Campbell ZT et al Cell Reports 2012]. The resulting compendium of specificities reveals the global RNA binding preferences of natural proteins and enables the design of new specificities. Using the recognition code, we design a protein to bind endogenous cyclin B1 mRNA in human cells. A chimeric protein consisting of the designed PUF protein fused to a translation activation domain specifically increases cyclin B1 protein levels, resulting in enhanced sensitivity to chemotherapeutic drugs. Our study provides a guide for rational design of engineered mRNA control, including translational stimulation.

Biography:

Abstract:

Our Laboratory of Personalized Genomic Medicine (LPGM) at Columbia University Medical Center started to offer clinical whole exome sequencing (WES) in January 2013. We processed and issued reports on over 500 cases mostly trios. Next-generation sequencing in the clinical practice allows for a critical review of the literature describing the pathogenicity of specific mutations or the disease relatedness of specific genes and also provides an important discovery tool for new disease genes and disease causing mutations. Because of the large volume and complex nature of the data obtained from large panels and whole exome sequencing testing, the management of the data in a transparent, yet powerful analytical framework is a key to successful clinical operation. Population allele frequency, data from parents and precise, yet concise phenotypic description are the cornerstone for successful clinical evaluation of the pathogenicity of variants identified. The full potential for discovery of new disease associated genes and disease causing mutations can only be realized if there is a tight collaborative effort between the clinicians performing the interpretation and structural biologists and analytical chemists and cell biologists who can help predict and verify the effects of variants identified. Through in my presentation the audience will obtain an understanding of the current state of the art of clinical genomic testing; will become familiar with the major factors that determine the precision and sensitivity of pathogenic mutation detection; have a thorough understanding of the importance of proper implementation of structural and functional basic science data sources into the clinical analysis pipeline. I will outline the contribution of clinical data collection to discoveries in basic science and review the obstacles to and opportunities for more efficient collaboration between clinical medical centers and the pharmaceutical industry.

Biography:

Hao Mei has completed his PhD from North Carolina State University with majors in Statistics and Bioinformatics and his Postdoctoral studies from Center for Human Genetics at Duke University. He is currently Associate Professor of University of Mississippi Medical Center and Professor of Shanghai Jiao Tong University. He is an Active Investigator of Jackson Heart Study and Atherosclerosis Risk in Communities Study and he has published more than 20 papers in reputed journals for genetic study of complex disease.

Abstract:

Genetic heritability and expression study have shown that different diabetes traits have common genetic components and pathways. The uniform-score gene-set analysis (USGSA) is a computationally efficient method for pathway enrichment test that unifies different gene measures by a uniform score for identifying pathways from genome-wide association and expression data and a R package of snp Gene Sets is implemented to facilitate the analysis. USGSA was applied to identify common pathways associated with diabetes traits based on public dbGaP GWAS results following a two-stage study strategy: the stage I of 11 Framingham Heart Study (FHS) GWAS and the stage II of 5 independent GWAS. The study identified 7 gene sets that contain binding motifs at promoter region of component genes for 5 transcription factors (TFs) of FOXO4, TCF3, NFAT, VSX1 and POU2F1 and microRNA of mir-218. These gene sets include 25 common genes that are among top 5% of the gene associations over genome for all GWAS. To further evaluate the identified diabetes pathways, 30 microarray data of different tissues was retrieved from the Gene Expression Omnibus. The USGSA with meta-analysis showed that 6 gene sets are also enriched for top 5% of the differential gene expressions. The pathway analysis suggested that different diabetes traits share common pathways and diabetes pathogenesis at varied tissues is potentially regulated by common TFs and microRNA.

Biography:

Prof. Igor A. Sobenin was born in 1962 in Russia. He has got his MD in 1988 (Chelyabinsk State Medical Institute, Russia), PhD in 1991 (Russian Endocrinology Research Center), and DSc in 2006 (Institute of General Pathology and Pathophysiology, Russia). Now he is a Leading Researcher at Russian Cardiology Research and Production Complex (Moscow, Russia). His research activity is in a field of molecular and cellular mechanisms of atherosclerosis, genetic and phenotypic markers of susceptibility, clinical, epidemiological and population studies in the field of atherosclerosis. He has over 200 published papers, among them over 120 are in international peer-reviewed journals.

Abstract:

In human pathology, several diseases are associated with mutations in the mitochondrial genome (mtDNA). Genetic predisposition plays an important role amidst the other risk factors in the development of atherosclerosis, a socially significant multifactorial disease. Even though mitochondrial dysfunction leads to increased oxidative stress, the role of mitochondrial mutations in atherosclerosis has not received much attention so far. Conclusions: The focality and mosaic character of atherosclerotic lesions in human aortic intima may be due to the differences in the heteroplasmy level of mtDNA mutations to a great extent, and a certain profile of pro- and antiatherosclerotic mutations of mitochondrial genome is characteristic for different types of atherosclerotic lesions. The presence of heteroplasmic non-synonymous mtDNA mutations may lead to mitochondrial dysfunction in specific sites of intimal tissue. The data obtained in clinical study can be used to assess individual risk of atherosclerosis, as well as for further studies on the role of mitochondrial genome mutations in the development of atherosclerosis and its clinical manifestations. The individual profile of certain mtDNA variants may partially explain atherosclerosis variability and genetic predisposition to atherosclerosis in population, which could be inherited by maternal line.

Biography:

Dr. Massey is an academic neuropharmacologist, life sciences professional, senior executive and entrepreneur with twenty-two years of experience. His experience encompasses executive management, operations, basic research, clinical affairs, regulatory affairs and marketing, in the pharmaceutical and biotechnology-related industries. He has played a leadership role placing 28 new drugs into human testing and 8 new drugs onto the market.

Abstract:

Advances in pharmacogenetic testing and personalized medicine are beginning to translate into clinical practice. The promise of these advances to improve patient outcomes and reduce cost of care are just being realized, however, an impediment to their rapid adoption has been the novelty of this information and the lack of understanding how to use it in normal clinical practice. As more pharmacogenetic discoveries are made, the information becomes more complex. This is especially true of combinatorial pharmacogenetics which considers multiple genes as they affect response to a particular drug. This lecture will provide a brief overview of pharmacogenetics with special attention to combinatorial pharmacogenetics and as to how this information can be used in clinical decision-making.

Biography:

Dr. Joyce Peng has established herself as a prominent voice for the application of state-of-the art technologies in the life sciences field. Joyce has been promoting bioinformatics and related products at various organizations including Oracle, Merck, Illumina and Life Technologies. Joyce is now marketing director at BGI, one of the largest genomics organizations in the world. Joyce’s marketing effort catapulted BGI from a company little-known outside of China to its current position as a global market leader in sequencing service in research and clinical markets. Joyce holds a Ph.D. in Biology from Caltech.

Abstract:

This talk gives an overview of how the world’s leading genomics institute, BGI, is applying state-of-the-art trans-omics technologies to advance human disease research and clinical diagnostics development. With the goal of translating medical research breakthroughs into global healthcare solutions, BGI is enabling medical providers and patients worldwide realize the promise of genomics-based diagnostics and personalized healthcare.

Biography:

Ernestina Valadez-Moctezuma is Doctor in Sciences from UNAM-Mexico. She is currently Professor and Researcher in Molecular Biology and Molecular Genetic Markers areas at the Universidad Autonoma Chapingo (Mexico). She has published over 50 scientific papers in various scientific journals and she has participated in different international meetings.

Abstract:

Little is known about Opuntia seed storage proteins and their contribution to the differentiation and systematic of genotypes. The variation between 102 genotypes of Mexican Opuntia was investigates using electrophoretic patterns SDS-PAGE of their seed total protein (STPs) and seed storage proteins (SSPs). Albumins and globulins were the most abundant protein fractions with contents that oscillated between 2.6 and 11.9 mg/mL and between 2.6 and 9.5 mg/mL respectively. These were followed by glutelins fraction (2.3-8.5 mg/mL) and prolamins as the lowest (1.1-7.9 mg/mL) of the four seed protein factions. Equally, STPs content varied between 1.13 and 7.12 mg/mL. Therefore, the total protein content and the different protein fractions were not found to be correlated with any of the seed morphological behaviors. However, regardless of variations in protein content estimated in seeds, the electrophoretic patterns of STPs and SSPs as revealed in their SDS-PAGE were not so variable. Furthermore, the individual analysis of each STPs or the SSPs analyses separately were not enough to differentiate Opuntia genotypes included in the study. The cluster and multivariate analyses indicated that there is no separation between accessions of species of the prickly pear (sweets fruits) and xoconostle (acidic fruits) even though the latter were grouped together. Based on biochemical markers analyzed herein, the need for revision of taxonomic assignment of genotypes belonging to the genus Opuntia was suggested.

Biography:

M.A. Sazonova graduated from Kharkov State University in 1986. She defended her PhD thesis in 1999. From 1986 to 2005 she worked in the laboratory of molecular genetics of Human Genetics Institute of Research Centre of Medical Genetics RAMS, investigating molecular genetic features of cystic fibrosis and the frequency of somatic mutations in gene K-ras in patients with adenocarcinoma of colon. Currently she is working as a senior researcher in the laboratory of angiopatology at Institute of General Pathology and Pathophysiology in Moscow, where she deals with the analysis of mitochondrial genome mutations in atherosclerosis. M.A. Sazonova has 115 publications.

Abstract:

Nowadays atherosclerosis is one of the most common diseases. It is a basis for the majority of cardiovascular pathologies. The aim of the present study was a detection of mitochondrial genome mutations associated with symptomless atherosclerotic lesions of carotid arteries in women. Three atherogenic mutations (C3256T, G14709A and G12315A) and two antiatherogenic ones (G13513A and G14846A), which are associated with symptomless (preclinical) atherosclerosis in women, were found.

Biography:

Dr. Gulnaz Javan graduated with a Ph.D. in Forensic Science from Istanbul University, Istanbul, Turkey in 2003. Her current projects employ next generation sequencing and flow cytometry, of cadaver tissues, microbial diversity in soil under decomposing cadavers, and entomology, to determine corpses’ PMIs. She received a $200,000 NSF grant for the project, "Life after Death - The Thanatomicrobiome.” Dr. Javan introduced a new term, Thanatomicrobiome, at the 66th Annual American Academy Forensic Science Meeting (AAFS) in 2014.

Abstract:

The study of the postmortem microbial transformations after human death has yet to be fully investigated. In the present study, a new term, thanatomicrobiome, which refers to the microbiome existing in the internal organs and blood of a human host after death, is introduced. The objectives of this study were to: (i) establish the best method for extracting and sampling DNA from four internal organs (liver, spleen, heart, and brain) and blood of cadavers with PMIs 20-240 hours using the Roche 454 platform; (ii) demonstrate that the method is feasible to survey the 16S rRNA genes of the microbiome using the Illumina MiSeq platform; and iii) compare the beta diversity of the microbiomes by cause of death and gender. The results of the first objective demonstrated that the conventional phenol/chloroform method, followed by bead-beating and ethanol precipitation, was superior for extracting thanatomicrobiome DNA from the four organ tissues and blood of cadavers. The results of the second objective showed that the thanatomicrobiome is similar among the organ tissues and blood sample of the same cadaver. Additionally, facultative anaerobic bacteria, such as Lactobacillus, predominate in organ tissues and blood samples of cadavers with short PMIs and obligate anaerobic bacteria such as Clostridium, predominate in cadavers with longer PMIs. The third objective demonstrated that there are observable trends among taxa of same gender and cause of death. To date, this is the first study of its kind to examine the microorganisms associated with internal organ tissues of cadavers using culture-independent methods.

Biography:

Tamer A Gheita (MD) is a Professor of Rheumatology & Clinical Immunology at Kasr Al-Ainy School of Medicine, Cairo University. He attained the EULAR Certifi cate for Rheumatic diseases, Zurich, Switzerland (2012) and is Editor-in-Chief of the Egyptian Rheumatologist (Elsevier). He is serving as an Editorial Board Member of the European and African Journals of Rheumatology, International Journal of Rheumatic Diseases and the Annals of Pediatric Rheumatology. He has published more than 80 papers in reputed journals and several books. He is a Consultant at many JCI accredited hospitals and shared in several medical convoys to underprivileged communities.

Abstract:

Objective: Th e aim of this work was to measure the level of serum Interleukin-23 (IL-23) and assess its genotypes in Behçets Disease (BD) patients and to study the clinical signifi cance and relation to disease activity. Patients & Methods: Fift y BD patients and 30 age and sex matched controls were included. Disease activity was assessed using BD Current Activity Form (BDCAF). Serum IL-23 was quantifi ed by ELISA and (rs17375018) genotyping performed by real time PCR-allelic discrimination technique. Results: Th e serum IL-23 level was signifi cantly higher in patients compared to the control (p<0.0001). Th e IL23 genotypes were comparable between patients and control. Genotype in neuro-Behçets patients was AA (5.3%), AG (36.8%) and GG in 57.9% and those without: AA (22.6%), AG (35.5%) and GG (41.9%). Th ose with uveitis had AA (8.3%), AG (33.3%), GG (58.3%) while those without had AA (23.1%), AG (38.5%) and GG (38.5%). Th e IL-23 level according to the three genotypes was insignifi cantly diff erent (p=0.18). Th e BDCAF was signifi cantly lower in those with AA genotype (1.88±1.13) compared to AG (2.06±1.39) and GG (3.17±1.49) (p=0.02). IL23 level signifi cantly correlated with the BDCAF (r=0.62, p<0.0001) and disease duration (r=0.42, p=0.002). Conclusion: Th is is the fi rst study to report the possible role played by IL-23 and its gene polymorphism in neuro-BD and not only uveitis with a signifi cant relation to disease activity, making both potential markers. Larger scale multi-centre longitudinal studies are required to confi rm its role in the pathogenesis of neuro-Behcet’s and its impact on response to therapy.

Biography:

Wenju Wang has completed his PhD from Peking Union Medical College and Postdoctoral studies from Institute of Zoology, Chinese Academy of Science. He is an Associate Professor of Cancer Immunotherapy at Yan’an Hospital of Kunming City and Yunnan Cell Biology & Clinical Translation Research Center. Currently, his researches focus on developing novel antigen-specifi c immune cells against tumors.

Abstract:

Clinical trials of Cytokine-Induced Killer (CIK) cells based immunotherapy against cancer are widely performed in China. However, the mechanism of CIK cell proliferation and acquisition of cytolytic function against tumor have not been well elucidated yet. We compared the proliferation and tumor toxic capacity between CIKIL-2 and CIKIL-15. By employing microarray, we analyzed miRNA expression profi les of PBMCs, CIKIL-2 and CIKIL-15. Moreover, RNA-seq was performed to identify diff erentially expressed genes between CIKIL-2 and CIKIL-15. Th e results indicated that CIKIL-15 showed improved cell proliferation capacity compared to CIKIL-2. However, CIKIL-2 has exhibited greater tumor cytotoxic eff ect than CIKIL-15. Bioinformatic analysis indicated that miR-143-3p/miR-145-5p was miRNA cluster which may positively regulated cell proliferation. In contrast, miR-340-5p/miR- 340-3p cluster may negatively regulate cell proliferation via induction apoptosis, which may cause decreased cell proliferation capacity of CIKIL-2. Importantly, we found that repressed miR-193a-5p may regulate the expressions of inhibitory receptor KLRD1 which may restrict cytotoxic function of CIK. Employing deep sequencing, a total of 374 diff erentially expressed genes (DEGs) were identifi ed. Among DEGs in CIKIL-15, Wnt signaling and cell adhesion were signifi cant GO terms and pathways which related with their functions. In CIKIL-2, type I interferon signaling and cytokine-cytokine receptor interaction were signifi cant GO terms and pathways. We found that inhibitory signal from interaction between CTLA4 and CD80 may be responsible for the weak proliferation capacity of CIKIL-2. Our fi ndings have provided new insights into mechanisms of CIK cells production and tumor cytotoxic function.

Biography:

Gopal B Krishnan completed his PhD from the National Institute of Immunology, New Delhi and has worked on Early Embryonic Development and Role of Bone Morphogenetic Proteins in his Post-doctoral Fellowship at the University of Wisconsin, Madison. Before joining Promega Corp, he worked as the Team Lead for Development of DNA and siRNA transfection reagents at Mirus Bio. Currently, he is a Global Product Manager of genomics products at Promega Corp., Madison, WI. He has published over thirty peer reviewed articles, chapters and abstracts. In addition he has successfully launched fi ve new life science research products.

Abstract:

Micro RNAs (miRNAs) along with small interfering RNAs and several classes of non-coding RNAs (example snRNA, snoRNA and piRNA) have widespread impact on a variety of biological processes. miRNAs are an important class of small RNAs that regulate gene expression. While most of the known mammalian miRNAs have been characterized using cloning and sequencing, there are still many with unknown functions. In general, the analysis of small RNAs and their expression is a critical part of many research studies due to the signifi cant role played by miRNA in controlling vital pathways such as growth, development and death. Much interest has been directed at studying the expression of miRNA in cells and tissues as well as bodily fl uids. Increasing eff ort is directed into bio-informatic prediction of new miRNA sequences. A combination of computational biology tools and molecular cloning methods is being used for characterizing additional miRNAs. However, isolating the mature miRNA fraction is the fi rst critical step in cloning these small regulatory molecules. Th e presentation will focus on tools developed to study small RNA including non-organic reagent based purifi cation methods that ensure high yields of pure RNA protected from RNase degradation and accurately quantify RNA to use in varied down-stream applications such as quantitative RT-PCR, arrays and sequencing. While most traditional RNA isolation methods are not very effi cient at recovering these smaller RNAs that contain 17-24 nucleotide mature miRNA, the RNA workfl ow employed along with this purifi cation method ensures high quality total RNA with enhanced miRNA enrichment from a variety of sample types.

Biography:

Peter Lajos Nagy is a biochemist and a physician, board certified in anatomic and molecular genetic pathology. His research focuses on the role of transcriptional processing in the pathogenesis of neurodegenerative disorders. He developed S. pombe and M. musculus models for Ataxia-Oculomotor-Apraxia type 2 (AOA2) caused by mutations in the human ortholog of the yeast RNA helicase Sen1, Senataxin (SETX). Using these models we are working to define the pathomechanism of SETX mediated neurodegenerative disorders AOA2 and ALS4.

Abstract:

Our Laboratory of Personalized Genomic Medicine (LPGM) at Columbia University Medical Center started to off er clinical Whole Exome Sequencing (WES) in January 2013. We processed and issued reports on over 500 cases mostly trios. Next-generation sequencing in the clinical practice allows for a critical review of the literature describing the pathogenicity of specifi c mutations or the disease relatedness of specifi c genes and also provides an important discovery tool for new disease genes and disease causing mutations. Because of the large volume and complex nature of the data obtained from large panels and whole exome sequencing testing, the management of the data in a transparent, yet powerful analytical framework is a key to successful clinical operation. Population allele frequency, data from parents and precise, yet concise phenotypic description are the corner-stone for successful clinical evaluation of the pathogenicity of variants identifi ed. Th e full potential for discovery of new disease associated genes and disease causing mutations can only be realized if there is a tight collaborative eff ort between the clinicians performing the interpretation and structural biologists and analytical chemists and cell biologists who can help predict and verify the eff ects of variants identifi ed. Th rough my presentation, the audience will obtain an understanding of the current state of the art of clinical genomic testing; will become familiar with the major factors that determine the precision and sensitivity of pathogenic mutation detection; have a thorough understanding of the importance of proper implementation of structural and functional basic science data sources into the clinical analysis pipeline. I will outline the contribution of clinical data collection to discoveries in basic science and review the obstacles to and opportunities for more effi cient collaboration between clinical medical centers and the pharmaceutical industry.

Biography:

Zuhier Awan is a Physician-Scientist at King Abdulaziz University and an Adjunct Professor at McGill University. He has completed a combined training in Internal Medicine and Medical Biochemistry at McGill University and a Postdoctoral Fellowship in Cardiovascular Genetics followed by a Fellowship in Preventive Cardiology and Advanced Clinical Lipidology. Later, he earned both MSc and PhD degrees with honors from the Department of Biochemistry and Molecular Medicine from University of Montreal and did his thesis in PCSK9 and the Prevention of Cardiometabolic Disease in Familial Hypercholesterolemia

Abstract:

Introduction: Th e chronicles of Familial Hypercholesterolemia (FH) in the Middle East started sixty years ago with the fi rst description of Essential Hypercholesterolemia in numerous Lebanese families by Khachadurian et al in 1962. Later, the fi eld of FH and atherosclerosis expanded exponentially with numerous reports of mutations. FH became the number one cause of genetic Cardio-Vascular Disease (CVD) worldwide. Method & Results: Th rough follow up and close observation of the status of FH in the Middle East and North African (MENA) countries have shown a global under reporting, poor management and premature death in obvious genetic FH cases. Furthermore, emergence of the third culprit PCSK9 gene associated with FH by eff orts of Middle Eastern scientists has fl ourished the concept. Finally, surveillance of FH cases had aided in the understanding of the incidence of aortic calcifi cation and the essential role of infl ammation as a neglected marker and target of therapy in these individuals. Conclusion: Eff orts to establish a registry and cascade screening for FH in the MENA countries is undergoing to improve the recognition of cases in the MENA communities, increase awareness of the number one genetic risk for CVD and prevent premature atherosclerosis in FH. Th is registry will positively identify novel FH mutations which will have remarkable implications in the care of FH in this region and the world.

Biography:

Cheng-Han Tsai has completed his PhD from National Yang-Ming University and now is the fi rst year Post-doctoral studies from the same institute. His studies focuses on changes of physiological characteristics as well as related genes profi le including miRNA of lung cancer cell in vitro and in vivo while the actin associated protein, ADF/cofi lin is manipulated. Some of studies have been published on reputed journals and other manuscripts are under prepared for further submissions

Abstract:

Cofi lin-1, a non-muscle isoform of actin regulatory protein that belongs to the actin-depolymerizing factor (ADF)/cofi lin family is known to aff ect cancer development. Previously, we found that over-expression of cofi lin-1 suppressed the growth and invasion of human Non-Small Cell Lung Cancer (NSCLC) cells in vitro. In this study, we further investigated whether overexpression of cofi lin-1 can suppress tumor growth in vivo, and performed a microRNA array analysis to better understand whether specifi c microRNA would be involved in this event. Th e results showed that over-expression of cofi lin-1 suppressed NSCLC tumor growth using the xenograft tumor model with the non-invasive reporter gene imaging modalities. Additionally, cell motility and invasion were signifi cantly suppressed by over-expressed cofi lin-1, and down-regulation of Matrix Metalloproteinase (MMPs) 1 and 3 was concomitantly detected. According to the microRNA array analysis, the let-7 family, particularly let-7b and let-7e, were apparently up-regulated among 248 microRNAs that were aff ected aft er over-expression of cofi lin-1 up to 7 days. Knock-down of let-7b or let-7e using chemical Locked Nucleic Acid (LNA) could recover the growth rate and the invasion of cofi lin-1 overexpressing cells. Next, the expression of c-myc, LIN28 and Twist-1 proteins known to regulate let-7 were analyzed in cofi lin-1 overexpressing cells, and Twist-1 was signifi cantly suppressed under this condition. Up-regulation of let-7 microRNA by overexpressed cofi lin-1 could be eliminated by co-transfected Twist-1 cDNA. Taken together, current data suggest that let-7 microRNA would be involved in over-expression of cofi lin-1 mediated tumor suppression in vitro and in vivo.

Biography:

Sazonova M A graduated from Kharkov State University in 1986. She defended her PhD thesis in 1999. From 1986 to 2005, she worked in the laboratory of molecular genetics of Human Genetics Institute of Research Centre of Medical Genetics RAMS, investigating molecular genetic features of cystic fi brosis and the frequency of somatic mutations in gene K-ras in patients with adenocarcinoma of colon. Currently, she is working as a Senior Researcher in the laboratory of angiopathology at Institute of General Pathology and Pathophysiology in Moscow, where she deals with the analysis of mitochondrial genome mutations in atherosclerosis. She has 115 publications to her credit.

Abstract:

Objective: Nowadays, atherosclerosis is one of the most common diseases. It is a basis for the majority of cardiovascular pathologies. Th e aim of the present study was a detection of mitochondrial genome mutations associated with symptomless atherosclerotic lesions of carotid arteries in women. Methods: Th e participants of the study were 183 conventionally healthy women from Moscow region, having no clinical manifestations of atherosclerosis in the form of coronary heart disease, old myocardial infarction or stroke. Th e age of the women varied from 34 to 86 years, the average age in the selection was 65.41(SD=9.34) years. High-resolution B-mode ultrasonography of carotids was used to estimate the extent of carotid atherosclerosis by measuring of the carotid Intima-Media Th ickness (cIMT). DNA samples were obtained from whole venous blood. In the present selection, 42 mitochondrial genome mutations were analyzed. Fragments of DNA were amplifi ed by PCR and further analyzed by new original method of quantitative assessment of mutant allele, developed in our laboratory on the basis of pyrosequence technology. Conclusion: Three atherogenic mutations (C3256T, G14709A and G12315A) and two anti-atherogenic ones (G13513A and G14846A), which are associated with symptomless (preclinical) atherosclerosis in women, were found.

Biography:

Patricia E Berg received her Bachelor’s degree in Mathematics from the University of Chicago, her PhD in Microbiology from the Illinois Institute of Technology then pursued Post-Doctoral studies at the University of Chicago. A research at the National Institutes of Health followed. Currently, she is a Professor of Biochemistry and Molecular Medicine at George Washington University in Washington, DC where she is Director of a Cancer Research Laboratory. Her work which centers on the BP1 gene has been published in major journals and has been featured on network television and in major media including the New York Times and Washington Post.

Abstract:

BP1, a gene we identifi ed and cloned is a member of the homeobox gene family of Transcription Factors (TF). BP1 is overexpressed in breast cancer, prostate cancer, ovarian cancer, acute myeloid leukemia, non-small cell lung cancer and possibly other malignancies as well. Important characteristics of BP1 in breast cancer include: (1) BP1 is expressed in 80% of invasive ductal breast tumors including 89% of the tumors of African American women compared with 57% of the tumors of Caucasian women. (2) BP1 expression correlates with the progression of breast tumors, from 0% in normal breast tissue to 21% in hyperplasia and 46% in ductal carcinoma in situ. (3) Expression of BP1 is associated with larger tumor size. (4) BP1 appears to be associated with metastasis. Forty-six cases of infl ammatory breast cancer were examined and all were positive for BP1 expression as well as matched lymph nodes in the nine metastatic cases. (5) BP1 overexpression induces oncogene expression including BCL-2, VEGF and c-MYC as well as other genes important in angiogenesis, invasion and metastasis. pBP1 down-regulates BRCA1 and (6) BP1 up-regulates ER alpha and induces estrogen independence. High pBP1 levels can lead to estrogen independence in ER positive breast cancer cells and tumors in mice. In summary, BP1 appears to confer properties on breast cancer cells that lead to a more invasive and aggressive phenotype. Since the functions of homeotic TF are highly conserved, it is likely that BP1 regulates many of the same processes and genes in other malignancies.

Biography:

Igor A Sobenin has got his MD in 1988 (Chelyabinsk State Medical Institute, Russia), PhD in 1991 (Russian Endocrinology Research Center), and DSc in 2006 (Institute of General Pathology and Pathophysiology, Russia). Now, he is a Leading Researcher at Russian Cardiology Research and Production Complex (Moscow, Russia). His research activity is in a fi eld of molecular and cellular mechanisms of atherosclerosis, genetic and phenotypic markers of susceptibility, clinical, epidemiological and population studies in the fi eld of atherosclerosis. He has over 200 published papers, among them over 120 are in international peer-reviewed journals.

Abstract:

In human pathology, several diseases are associated with mutations in the mitochondrial genome (mtDNA). Genetic predisposition plays an important role amidst the other risk factors in the development of atherosclerosis, a socially signifi cant multifactorial disease. Even though mitochondrial dysfunction leads to increased oxidative stress, the role of mitochondrial mutations in atherosclerosis has not received much attention so far. Conclusions: Th e focality and mosaic character of atherosclerotic lesions in human aortic intima may be due to the diff erences in the heteroplasmy level of mtDNA mutations to a great extent, and a certain profile of pro and anti-atherosclerotic mutations of mitochondrial genome is characteristic for diff erent types of atherosclerotic lesions. Th e presence of heteroplasmic nonsynonymous mtDNA mutations may lead to mitochondrial dysfunction in specifi c sites of intimal tissue. Th e data obtained in clinical study can be used to assess individual risk of atherosclerosis, as well as for further studies on the role of mitochondrial genome mutations in the development of atherosclerosis and its clinical manifestations. Th e individual profi le of certain mtDNA variants may partially explain atherosclerosis variability and genetic predisposition to atherosclerosis in population, which could be inherited by maternal line.

Biography:

Afsheen Arif has completed her Ph.D. (Biotechnology) in 2013 from The Karachi Institute of Biotechnology and Genetic Engineering, KIBGE, University of Karachi and currently working as an Assistant Professor. She had more than 12 years of research experience. She has expertise in biotechnology, genetics and molecular biology. Research is her passion and she has keen interests are to study molecular genetics of rare diseases. She has ten publications in reputed journals. In Future, She would like establish stem cell and regenerative medicine laboratory.

Abstract:

Congenital heart diseases (CHDs) are the most common of all birth defects and one of the leading causes of mortality in the fi rst year of life. CFC1 gene is a cell signaling protein and it is a co-receptor in nodal signaling pathway and involve in right and left axis determination during gastrulation. Th is is a case control study, recruited 175 non syndromic patients and 140 controls, healthy unrelated individuals. Th e study aft er formal approval includes patients from various pediatric cardiology centers in three years. A detailed family history was taken to elucidate the genetic and environmental factors. Pediatric cardiologist confi rmed the diagnosis on the basis of all standard testing like chest X-ray, CBC, ECG, ECHO, heart murmur, cardiac catherization reports etc. DNA extraction and sequencing was done and data was interpreted by multiple sequence alignment soft ware. Statistical data was done by SPSS 17.0. Th e mean age for controls was 3.14±1.82 years for TOF; 2.97±1.21 and for DTGA patients 1.84±2.26 years. TOF and DTGA were frequent in males. Th e study demonstrates frequency of this disease with its variation in Pakistani population. Consanguinity aff ects the rate of CHDs as it is 62% in patients and 25% in controls. Two novel mutations were found in CFC 1 gene. Th e study reveals frequency and prevalence for TOF and DTGA, their variation and association with other cardiac defects. CFC1 and its mutations may play a key role in cardiac malformation.

Biography:

K. Paul Marx have completed my MSc (Medical Biochemistry), MBA (Hospital Administration) and finally pursuing Ph.D from Osmania University. His research work includes study on Biomarkers and Molecular markers, Polymorphism studies on Malaria. He has vast experience in clinical laboratory and well trained in estimation of Serum Procalcitonin and gained experience in techniques like Flow Cytometer (ARYA –II), PCR, RT-PCR, MALDI-TOF, SDS- PAGE, chromatography, protein purification and other molecular biology techniques. He has been selected by Govt of India for Basic Science Research Fellowship Program. He has also to his credit availing travel grant from Department of Biotechnology, DBT for attending the Genomics Conference. He has 7 research papers published in different National and International Journals and now yet to communicate more papers to his credit. He has the ability to handle research problems independently and familiar with the current literature. He possesses a cheerful disposition and a cool temperament.

Abstract:

Malaria is a global health problem and its incidence is more prevalent in socio economically backward countries and developing countries like India. Gold standard microscopy for diagnosing malaria is choice for most clinicians. However among the newest biomarker, PCT has its own value in monitoring the severity of malaria and can be used for therapeutic management as well with highest diagnostic accuracy. PCT levels rise rapidly (within 6–12 hours) aft er an infectious insult with systemic consequences. Daily changes of plasma PCT levels give an indication of the course of the disease and the prognosis of the patient. Persistently elevated levels of PCT are associated with poor outcome and are now viewed as a failure of therapy or the lack of appropriate clearance of source of the infection. In the present investigation PCT was quantitatively analyzed along with conventional hematology and biochemical parameters and response to treatment was validated by PCT measurement in consecutive samples of both uncomplicated and severe malaria. Many studies have demonstrated that SNP’s in genes may not only aff ect the expression or activities of the enzymes or proteins but are associated with the risk of diff erent types of malaria. Since PCT is a product of CALC1 gene, we analysed CALC 1 -624T/C promoter polymorphism in malaria to disentangle their role with PCT as a marker for enhanced disease severity. Our fi ndings indicate that PCT in plasma of malaria patients positively correlated with platelet count, WBC, Neutrophil (p value 0.001). We have found strong association between serum PCT levels and neutrophil toxic granules and their usefulness as surrogate biomarkers in the management of malaria patients. In conclusion, our fi ndings indicate that persistently increased levels of PCT were always indicative of an unfavourable outcome and hidden parasitemia. Initial high levels of PCT were indicative of a more severe disease status (parasitemia, P value <0.001) and this refl ected in a longer patient stay predicting adverse outcomes. From our observations it can also be concluded that -624T/C polymorphism may be related to higher risk of malaria in Indian population. So in current scenario, addition of various and reliable biomarkers to the standard work-up of patients with good publicity could increase diagnostic certainty and improve patient’s management by administering proper therapies to the right patient at the right time thus guarantying full recovery, post hospital discharge.

Biography:

Gehan Hamdy has completed here MBBCh from Kasr El Ani Hospital, Cairo University, Egypt and Postdoctoral studies from same University. She is Assistant Professor of Internal Medicine. She has published more than 10 papers and 3 case reports in reputed journals.

Abstract:

Background: Th e identifi cation of additional genetic risk factor is an on-going process that will aid in the understanding of Rheumatoid Arthritis (RA) aetiology. A genome-wide association scan in Crohn’s Disease (CD) highlighted the Interleukin-23 Receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesized that IL23R could be a shared susceptibility gene. Th e rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyze IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients. Methods: A group of Egyptian patients with RA (n=120) and apparently healthy persons as controls (n=120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the fi rst SNP and restriction fragment length polymorphism/PCR (RFLP/ PCR) in the last two SNPs. Results: Our data emphasise that the AA genotype of rs11209026 (Arg381Gln) was signifi cantly associated with RA patients compared to the controls (p value=0.001). We did not fi nd any signifi cant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (p value=1.000 & 0.562, respectively). Conclusion: Our results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the sub-group of patients who will benefi t from the selective suppression of the IL23 signaling which would represent new perspectives toward a personalized therapy of RA patients by further studies.

Biography:

John M Rosenfeld received his BS from Georgetown University, and received his PhD in molecular biology & biochemistry from the University of California, Irvine. He performed his Post-Doctoral training in the laboratory of Dr Ronald Evans at the Salk Institute on the topic of profi ling transcriptional targets of orphan nuclear receptors. He joined Merck-Millipore in 2003, and has been developing research tools to explore gene regulation for the past 11 years. In addition to developing research tools and assays for epigenetic analysis, he is now responsible for managing platform technology development and external innovation for EMD Millipore and is part of the bioscience scientifi c networking group in this company.

Abstract:

Chromatin immune-precipitation provides an in vivo picture of protein association within the dynamic cellular chromatin environment. Over the past decade, additional resolution on chromatin structure has been elucidated using other techniques that capture proteins or nucleic acids to uncover the composition of the components of chromatin, including regulatory proteins, modifi ed histones, modifi ed genomic DNA and the new putative chromatin regulatory molecule, non-coding RNAs. Th ese precipitation techniques, both immune based as well as nucleic acid capture based, allow dissection of the role of these molecules in establishing and characterizing chromatin state. Th e methods can be easily combined with current library construction techniques to provide genome wide views of these interactions under experimental treatments & genetic backgrounds. Th e information provided by ChIP (Chromatin Immuno-Precipitation), Nuclear RIP (RNA Binding Protein Immuno-Precipitation of chromatin) and ChIRP (Chromatin Isolation by RNA ) will be discussed.

Biography:

Maarten Rudolph Leerkes is an accomplished Bioinformatics Scientist at NIH-BCBB (Bioinformatics and Computational Biosciences Branch). He works on developing novel quantitative biology methods. He has worked on identifying molecular signatures for disease prognosis and treatment prediction in patient sub-populations in biotech industry as well as on product development including study design for product validation in clinical settings. His PhD, Post-doctoral and research experiences span academia as well as biotech industry settings where he focused on the use of bioinformatics to interpret sequencing data (NGS) and to fi nd patterns that can be extrapolated into diagnostic tools for improving treatment for patients.

Abstract:

We have analyzed RNAseq data in the context of re-annotating the genome of African green Monkeys (AGM). RNA-seq experiments were designed to answer questions regarding the mechanisms underlying the lack of disease progression in these natural Simian Immunodefi ciency Virus (SIV) hosts which are still poorly understood. Although the AGM genome is available, it is poorly annotated. Th e rhesus genome is also available for dual-genome predictions and although it has its own limitations, it can be used in combination with RNA-seq data to re-annotate the AGM genome. Th e patas monkey is an interesting third primate study model but does not have a reference genome available and depends on de novo assembly of RNA-seq reads to be analyzed. De novo assembly compared with genome-based splicing detection helps cross-validate methods. Cross-species comparisons can shed light in more detail on resistance mechanisms related to SIV and HIV infections. RNA-seq studies focusing on splicing signatures are an essential tool for both genome re-annotation and biomarker discovery. As such, this is of interest for upcoming RNA-seq studies with the objective to more accurately defi ne how specifi c splicing signatures render African green monkeys resistant to progressive SIVagm infection. Th is is promising in the discovery of novel molecular targets in the process of SIV infection and can serve as a model for human HIV targets and thus serves as a compelling example that impacts genomic advances on global health.

Biography:

Huijuan Wang has graduated from Northwest University of China and received her PhD degree in Biochemistry and Molecular biology. Since 2011, she was recruited as a Teaching Staff by College of Life Science, Northwest University mainly focuses on the clinical application of pharmacogenomics fi ndings in disease treatment especially cancers including development of genotyping methods and reagents for drug-related biomarkers and mechanic study of cancer-related biomarkers. Besides, lots of efforts are also dedicated on the study of the molecular mechanism underlying the resistance of anticancer drugs such as BRAF inhibitors and endocrine therapy.

Abstract:

Aims: HLA-B*58:01 is strongly associated with allopurinol induced Severe Cutaneous Adverse Reactions (SCARs). Th e aim of this study was to develop a new, convenient and economical method for HLA-B*58:01 genotyping and to investigate the distribution of HLA-B*58:01 in diff erent Chinese populations. Methods: Combined with ARMS (Amplifi cation Refractory Mutation System) primers and TaqMan probe, a single-tube duplex real-time PCR assay for HLA-B*58:01 typing was established with ACTB as an internal control. Using this method, the prevalence of HLA-B*58:01 in 349 samples including 100 Northern Chinese Han, 100 Buyei, 99 Tibetan and 50 Uighur were determined. Th e reliability and specifi city was assessed by comparison of genotyping results in 100 Buyei samples with Sequence-Based Typing (SBT). Meanwhile, the linkage status of rs9263726 in PSORS1C2 with HLA-B*58:01 in four Chinese populations was analyzed. Results: Th e HLA-B*58:01 genotyping result in 100 Buyei samples by real-time PCR was in 100% concordance with SBT and the detecting limit of this assay was 50 pg. Th e frequency of the HLA-B*58:01 allele in Buyei minority (17%) was signifi cantly higher than that in Han (4%), Tibetan (5.1%) and Uighur (2%) populations (p<0.05). Th e complete linkage of HLA-B*58:01 with SNP rs9263726 previously reported in a Japanese population was not observed in the Chinese populations. Conclusion: Th e newly developed assay proves to be rapid, cost-eff ective and reliable for HLA-B*58:01 detection prior to allopurinol administration. Meanwhile, the rs9263726 could not be used as an alternative marker to HLA-B*58:01 in clinical diagnosis for allopurinol-induced SCAR especially in Chinese populations.

Biography:

Luciano Brocchieri has completed his PhD in evolutionary biology at the Unversity of Parma (Italy) in 1992 and Postdoctoral studies at Stanford University, Department of Mathematics, in 1996. He was Senior Scientist at the Math Department in Stanford University and is currently Assistant Professor at the Department of Molecular Genetics and Microbiology, University of Florida. He has been invited at several international conferences and has published about fi fty papers in highly reputed international scientifi c journals. He is best known for his work in computational sequence analysis, protein evolution, and gene identification.

Abstract:

Gene annotation in prokaryotic genomes is challenged by inconsistencies among gene predictors and by incomplete or ambiguous information from evolutionary conservation, and recent analyses have evidenced the existence of genes missing from 1000 genome annotations. Popular gene prediction methods predict in the same genomes almost 20% more genes that are not in the annotations. Although for the majority of the excluded genes there is no convincing evidence of conservation, justifying their exclusion from annotations, we identifi ed among excluded genes a substantial fraction of genes conserved in sequence and in length across genera or phyla, many of which are corroborated by all methods. Introducing the N-PACT (N-Profi le Analysis Computational Tool) methods, we found that several of these ORFs could also be identifi ed by their signifi cant compositional periodicity. From information from gene prediction, evolutionary conservation and sequence 3-base periodicity, we estimated that as much as 30% of the currently annotated genomic inter-genic space could be occupied by unrecognized coding regions. We verifi ed expression of predicted genes in Pseudomonas aeruginosa PAO1 by RIBO-seq analysis, the genome-wide sequencing of mRNA regions undergoing translation by ribosome foot-printing. From the analysis of ribosome-footprint distributions, we could confi rm expression of the majoirity of the annotated genes, provide evidence of some mis-predicted starts-of-translation, and verifi ed expression of many predicted genes not included in the published annotation. Furthermore, ribosome footprints provided evidence of the existence of coding regions not predicted by any method, of previously unrecognized mechanisms of post-transcriptional regulation of translation (‘leader peptides’), as well as of alternative translational products.

Biography:

Alexander Kaplun has completed his PhD from Ben Gurion University and Postdoctoral studies from Karmanos Cancer Institute. He is a Senior Scientist, Advanced Genomics Integrated Solutions at QIAGEN Bioinformatics, Global Leader in development and distribution of clinical and biological software tools and databases. He has published more than 20 papers in peer-reviewed journals.

Abstract:

The Pharmaco-Genomic Mutation Database (PGMD) is a comprehensive manually curated pharmaco-genomics database. Th e aim of this database is to provide a comprehensive resource for all variants that have been reported to have a pharmacogenomic eff ect in human studies and to describe those variants by exact genomic location and sequence alterations for application to NGS data analysis. Th e database is designed to contain extensive information as evidence for these associations including provenance of every observation. Two major sources of PGMD data are peer reviewed literature and FDA drug labels. PGMD curators capture information on exact genomic location and sequence changes resulting phenotype, drugs administered, patient population, study design, disease context, statistical signifi cance and other properties of reported pharmaco-genomic variants. Variants are annotated into functional categories basing on their infl uence on pharmacokinetics, pharmacodynamics, effi cacy or clinical outcome. Th e current release of PGMD includes nearly 140000 unique pharmaco-genomic observations, covering all 24 disease super classes and 1377 drugs. Over 2800 genes have associated pharmaco-genomic variants including genes in proximity to intergenic variants. PGMD is optimized for use in annotating next generation sequencing data by providing genomic coordinates for all covered variants including SNPs, insertions, deletions, haplotypes, diplotypes, VNTRs, copy number variations and structural variations.

Biography:

Haidan M Salem is an Academic Lecturer of Molecular Biology and Genetics and completed her PhD in 2014 at Cairo University, Egypt. Currently, she is supervising one PhD thesis and four MSc theses, working on two projects entitled "Investigation of the possible role of par-4 as a therapeutic pro-apoptotic protein in hepatocellular carcinoma" and "Effi ciency of using Camptothecin and 7-hydroxy-6-methoxycoumarin encapsulated in chitosan nanoparticles in Hepatocellular carcinoma treatment”. She has taught a number of biology courses, a number of practical molecular and cytogenetic assays and also has an extensive experience working with DNA, RNA and proteins.

Abstract:

Increase using of nanoparticles in the industry ranging from health care products to cosmetics to dietary supplements let human exposure to nanoparticles is a driving concern. TiO2 nanoparticles are used in a broad range of applications due to their high stability, corrosion resistance and photocatalytic properties. Recent evidences have shown TiO2 nanoparticles to induce inflammatory and genotoxic response in diff erent animal and human cell lines. However, the mechanisms involved in nano- TiO2 induced genotoxicity and carcinogenicity have not been clearly defi ned and are poorly studied in vivo. Ras gene is a protooncogene that normally regulate the cell proliferation, the aim of the present study is to evaluate point mutation that may be induced by diff erent treatments (acute and sub-acute) and doses of titanium dioxide nanoparticles TiO2 (<100 nm) in testis, lung and kidney of mice in Ha-ras gene exons 2 and 3 (hot spot exons) as an example of oncogenes using PCR-Single-Strand Conformation Polymorphism (SSCP) analysis and sequencing of the mutant samples. Sequencing of mutant samples revealed substitution mutations caused amino acid substitution and insertion mutations caused frame shift and insertion mutations found outside coding sequence. In conclusion, Single Strand Conformation Polymorphism (SSCP) analysis of Ha-ras exons 2, 3 and sequencing studies showed that TiO2 nanoparticles signifi cantly increased the incidence of band alterations and induced diff erent point mutations at diff erent dose levels and treatments in lung, kidney and testis compared to control. Anyway, further investigation should be considered to fi gure out the possible role of long exposure of TiO2-NPs in cancer initiation.

Biography:

Hao Mei has completed his PhD from North Carolina State University with majors in Statistics and Bioinformatics and his Postdoctoral studies from Center for Human Genetics at Duke University. He is currently Associate Professor of University of Mississippi Medical Center and Professor of Shanghai Jiao Tong University. He is an Active Investigator of Jackson Heart Study and Atherosclerosis Risk in Communities Study and he has published more than 20 papers in reputed journals for genetic study of complex disease.

Abstract:

Genetic heritability and expression study have shown that diff erent diabetes traits have common genetic components and pathways. Th e Uniform-Score Gene-Set Analysis (USGSA) is a computationally effi cient method for pathway enrichment test that unifi es diff erent gene measures by a uniform score for identifying pathways from genome-wide association and expression data and an R package of snp Gene Sets is implemented to facilitate the analysis. USGSA was applied to identify common pathways associated with diabetes traits based on public dbGaP GWAS results following a two-stage study strategy: the stage I of 11 Framingham Heart Study (FHS) GWAS and the stage II of 5 independent GWAS. Th e study identifi ed 7 gene sets that contain binding motifs at promoter region of component genes for 5 Transcription Factors (TFs) of FOXO4, TCF3, NFAT, VSX1 and POU2F1 and microRNA of mir-218. Th ese gene sets include 25 common genes that are among top 5% of the gene associations over genome for all GWAS. To further evaluate the identifi ed diabetes pathways, 30 microarray data of diff erent tissues was retrieved from the Gene Expression Omnibus. Th e USGSA with meta-analysis showed that 6 gene sets are also enriched for top 5% of the diff erential gene expressions. Th e pathway analysis suggested that diff erent diabetes traits share common pathways and diabetes pathogenesis at varied tissues is potentially regulated by common TFs and microRNA.

Biography:

Rana Ahmed Youness has completed her MSc degree from German University in Cairo (GUC) under the supervision of Professor Dr Ahmed Ihab Abdelaziz, Founder of the Molecular Pathology Research Group (MPRG).

Abstract:

Insulin-like Growth Factor-1 Receptor (IGF-1R) activation is a hallmark in Hepato-Cellular Carcinoma (HCC), stimulating several mitogenic signaling pathways most importantly PI3K/Akt/mTOR pathway. As an essential cornerstone of the innate immune system, Natural Killer (NK) cells are recognized as the fi rst native defender against HCC. Intersentingly, NK cells are among the immune cells with the highest level of IGF-1R and it was also reported to have a prominent role in NK cell differentiation. NK cells are known to be activated by the activating receptor, NKG2D, mediating its cytotoxicity mainly through perforins release. IGF-1R expression was found to be regulated by several miRNAs. However, miR-486-5p has never been investigated in HCC. So, the aim of this study was to control the HCC tumor progression through the direct impact of miR-486-5p on NK cells as well as their target hepatocytes in an immunotherapeutic approach. Huh7 cells were cultured and NK cells were isolated from 27 HCC patients. Both cell types were transfected by miR-486-5p using lipofection. Total RNA was extracted and quantifi ed using qRTPCR. Viability and proliferation analysis were performed using MTT and BrdU assays. miR-486-5p showed signifi cant down regulation of both IGF-1R and its down-stream oncoprotein mTOR in Huh7 cells and consquently, Huh-7 cellular viability and proliferation were repressed. Upon ectopic expression of miR-486-5p in NK cells of HCC patients both NKG2D and perforins expression were signifi cantly elevated. However, a signifi cant down-regulation of IGF-1R and mTOR were observed. In conclusion, it was shown that miR-486-5p has a dual role in enhancing NK cell cytotoxicity and harnessing the tumor progression of its target hepatocyte mainly through tuning essential members of IGF-axis.

Biography:

Daniel Rotroff is a Post-doctoral Research Scholar working with Motsinger-Reif in the Bioinformatics Research Center at NCSU. He has obtained a Master of Science degree in Public Health in 2010 and a PhD in Environmental Science and Engineering from the University of North Carolina at Chapel Hill in 2013. He has authored 20 publications that have accrued over 800 academic citations and his current research focuses on Assessing in utero epigenetic modifi cation due to maternal smoking, using metabolomics approaches for biomarker discovery and identifying genetic variants associated with drug-response phenotypes.

Abstract:

Cardio-Vascular Disease (CVD) is the leading cause of death worldwide. Individuals with type-2 diabetes are at an increased risk of CVD and alterations in total cholesterol (TC), LDL, HDL and triglycerides (TG) are known risk factors of CVD. Fenofi brate is a commonly prescribed cholesterol lowering drug but there is heterogeneity in treatment response. Here we conduct a genomewide association study to investigate common and rare genetic variants associated with lipid changes in 1261 diabetics from the ACCORD clinical trial for ~90 days of fenofi brate treatment. Analysis was also stratifi ed by white (n=773) and black (n=123) subjects. A total of 26, 35 and 120 common variants, mapping to 5, 7 and 24 genes were associated with change in TC, LDL, HDL and or TG in all races, white and black respectively (p<1×10-6). In addition, 7 genes were associated with changes in TG in the rare variant analysis (q<0.05). Signifi cant genes in the common and rare variant analysis were tested for gene expression changes in mice treated with fenofi brate. Th e validation study found 3 genes in the common variant analysis (SMAD3, ATP13A1 and IPO11) displayed signifi cantly decreased gene expression in mice treated with fenofi brate (q<0.25). RAB27B and DCUN1D4 were signifi cantly associated with TG in the rare variant analysis and displayed signifi cantly decreased and increased gene expression respectively. SMAD3 is an intracellular mediator of TGFβ and SMAD3-KO mice have been known to have increased insulin sensitivity and reduced adiposity. Th ese results may provide new biomarkers for fenofi brate drug response and lead to new therapeutic targets.

Biography:

Aditi Nadkarni is an Associate Research Scientist at New York University’s Department of Biology where she conducts research in the fi elds of carcinogenesis, DNA repair and genomics using human cells. Her previous work includes preclinical analysis of DNA repair inhibitors in glioma cells during a Post-doctoral Fellowship at Mayo Clinic and characterization of a breast cancer genetic mutant during her PhD research at University of Toledo.

Abstract:

Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) can give rise to DNA adducts that alter essential cellular functions such as replication and transcription and induce genome instability. DNA repair mitigates the deleterious eff ects of DNA damage. Nucleotide Excision Repair (NER) detects and removes bulky DNA adducts that disrupt base pairing and distort the DNA helix whereas Transcription-Coupled DNA Repair (TCR) removes DNA adducts that impede RNA polymerase elongation during gene expression. Site-specifi c DNA lesions were used to examine the relationship between NER and TCR in the repair of PAH-induced adducts. In addition, the consequences to gene expression and mRNA integrity of damage that escapes repair or is repaired slowly was also studied. Th e results indicate that TCR slowly repairs DNA adducts that block transcription but escape removal by NER. Furthermore, the absence of NER or TCR in cells defective in either or both pathways results in decreased gene expression and alterations to the sequence of the mRNA produced. Th ese fi ndings enhance our understanding of DNA repair and its role in processing DNA damage that impedes gene expression in human cells.

Biography:

Gerald J Wyckoff is a Molecular Evolutionary Geneticist. He was trained in fi nding faint signatures of positive selection in a sea of genomic noise. This led him to become involved with large scale genomic, and later proteomic, projects and these are his areas of interest. This has allowed him to extend his knowledge in drug discovery towards chemical information signatures for high-throughput screening of compounds.

Abstract:

We have established a rapid and practical methodology for the clustering of small molecule similarity. Th is is a known technique for analysis of next-gen sequence, expression data and other types of “big data”. However, this technique has not been deployed for small molecules because there has not been a good methodology for representing chemical similarity that lends itself to clustering across broad ranges of molecule similarity. We have developed a chemical fi ngerprinting system from earlier work that gives a bitwise score or “signature” for any molecule that can be represented in three-dimensional space (normally in a PDB or PDBQT fi le). Because of this, the mathematical difference between two small molecules bitwise scores acts as a traditional ‘distance” measure would enabling clustering of small molecules. When matched with traditional protein phylogenetic clustering, we derive a “sparse matrix” graph. Th e X-axis is populated by clustered small molecules; the Y-axis is populated by phylogenetically clustered protein targets. In the center of the graph, we record if a small molecule is known to interact with a specifi c protein target. Th ese graphs enable drug discovery. Structure-based virtual screening is an important tool in the drug discovery process. Th e use of computational tools has allowed for the screening of large libraries of chemical compounds to identify putative ligand-receptor interactions. Th e identifi cation of valid targets and therapeutic compounds has long-term importance both to public health and the economic strength of the pharmaceutical industry. Extending this technology by enabling small molecule clustering and results visualization is the next logical evolution of the technology.

Biography:

Gulnaz T Javan graduated with a PhD in Forensic Science from Istanbul University, Istanbul, Turkey in 2003. Her current projects employ next generation sequencing and fl ow cytometry, of cadaver tissues, microbial diversity in soil under decomposing cadavers, and entomology, to determine corpses’ PMIs. She received a $200,000 NSF grant for the project, "Life after Death - The Thanatomicrobiome.” She introduced a new term, Thanatomicrobiome, at the 66th Annual American Academy Forensic Science Meeting (AAFS) in 2014.

Abstract:

The study of the postmortem microbial transformations aft er human death has yet to be fully investigated. In the present study, a new term, ‘thanatomicrobiome’, which refers to the microbiome existing in the internal organs and blood of a human host aft er death, is introduced. The objectives of this study were to (i) establish the best method for extracting and sampling DNA from four internal organs (liver, spleen, heart, and brain) and blood of cadavers with PMIs 20-240 hours using the Roche 454 platform; (ii) demonstrate that the method is feasible to survey the 16S rRNA genes of the microbiome using the IlluminaMiSeq platform; and (iii) compare the beta diversity of the microbiomes by cause of death and gender. Th e results of the fi rst objective demonstrated that the conventional phenol/chloroform method, followed by bead-beating and ethanol precipitation, was superior for extracting thanatomicrobiome DNA from the four organ tissues and blood of cadavers. Th e results of the second objective showed that the thanatomicrobiome is similar among the organ tissues and blood sample of the same cadaver. Additionally, facultative anaerobic bacteria, such as Lactobacillus, predominate in organ tissues and blood samples of cadavers with short PMIs and obligate anaerobic bacteria such as Clostridium, predominate in cadavers with longer PMIs. Th e third objective demonstrated that there are observable trends among taxa of same gender and cause of death. To date, this is the fi rst study of its kind to examine the microorganisms associated with internal organ tissues of cadavers using culture-independent methods.

Biography:

Heba Bassiony is an Assistant Lecturer at Zoology department, Faculty of Science; Cairo University. She has completed her PhD recently in 2015 from Faculty of Science, Cairo University in the fi eld of cytology and molecular biology. She has published two papers in reputed journals and third paper is in submission. She is interested in cancer research and molecular biology.

Abstract:

Magnetite Nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study, we used Ehrlich Solid Carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. MNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. Our results revealed that tumor growth was signifi cantly reduced by IT and IP MNPs injection compared to untreated tumor. A signifi cant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. Th is increase was accompanied with increase in p53 protein expression. It is worth mentioning that no signifi cant diff erence in expression of p53 and p16 could be detected between IT ESC and control group. MNPs might be more eff ective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

Biography:

Daniel J Cooper has completed his PhD in Cell and Molecular Biology at the University of Texas at San Antonio in May of 2015, focusing on mechanisms maintaining genetic integrity in pluripotent stem cells. He is currently a Postdoctoral Associate at the University of Miami Miller School of Medicine’s Project to Cure Paralysis.

Abstract:

One important but poorly characterized aspect of stem cells is their ability to maintain genetic integrity while pluripotent, when induced to diff erentiate and or when derived from diff erentiated cells by reprogramming. We tested the hypothesis that pluripotency and enhanced genetic integrity are mechanistically linked at the genomic level. We used computational methods to mine previously published databases describing gene expression in human and mouse ES, iPS and diff erentiated cells and found that 40-44% of DNA repair genes are up-regulated in ES and iPS cells while only 1-13% are down-regulated. Cell death genes showed overall diff erential expression between pluripotent and diff erentiated cells with 14-24% of genes downregulated and 12- 23% up-regulated in pluripotent cells. We then used Ingenuity Pathway Analysis (IPA) to examine direct interactions between three pluripotency factors, SOX2, OCT4 and NANOG and these diff erentially expressed genes. In addition, we examined interactions between pluripotency factors and intermediary transcription factors that are themselves, regulated by pluripotency factors and which in turn regulate downstream genetic integrity genes. Th e combination of direct and indirect interactions we detected accounted for regulation of 22-50% of diff erentially expressed genetic integrity genes by the three pluripotency factors investigated. Several of the pluripotency-genetic integrity network interactions predicted by computational methods were subsequently validated by ChIP-qPCR. Taken together, our data support our hypothesis that enhanced maintenance of genetic integrity is mechanistically linked to the epigenetic state of pluripotency at the genomic level. In addition, these fi ndings demonstrate how a small number of key factors can regulate large numbers of downstream genes.

Biography:

Jumoke Soyemi completed her BSc (Computer Science) at Obafemi Awolowo University, Ile-Ife in 1999, MSc (Computer Science) at University of Ibadan in 2004 and is presently pursuing her PhD (Bioinformatics) at Covenant University, Ota under the Covenant University Bioinformatics Research cluster (CUBRe). Her PhD is supported by h3abionet grant.

Abstract:

Computational pharmacology is the application of bioinformatics and computational biology with relevance to pharmacology including understanding of drug action, adverse drug reaction, identification of drug targets and drug design. Early and accurate identifi cation of Adverse Drug Reactions (ADR) is critically important for drug development and clinical safety. Oft en times the adverse eff ect of drugs are not discovered until years later aft er the drugs’ release to the market. Th e post hoc analysis is usually unable to detect rare or delayed on-set ADR until clinical evidence accumulates. Th e process of drug development and ADRs discovery takes years, meaning that a lot of harm would have been caused to lives before evidences are accumulated, therefore developing a computational pharmacology model that can be used to make informed decisions to decrease attrition rate in the process of drug development with improve number of drugs having an acceptable benefi t and risk ratio is paramount. Th is paper reviews and compares computational methods of the few works that has been done so far to address this issue and hence looks at the applicable methods that can be used in drug to ADR prediction.

Biography:

Binay Kumar Raut is working as a Lecturer in Biochemistry at Kathmandu University School of Medical Sciences, Nepal. He is interested to conduct research in Biochemistry. He authored many publications which mainly concentrates prevalence of iron deficiency in Pregnant women and Oncogenes responsible for Bone Marrow Cancer.

Abstract:

Background: Leukemia is a neoplastic proliferation of hematopoietic cells. Leukemia can be classifi ed as either myelocytic (myeloid) or lymphocytic (lymphoid) depending on the lineage of the leukemic cells and chronic and acute depending on the clinical course. Aim: Th e aim of the present study was to detect structural abnormalities by using automated karyotyping (IKAROS) soft ware in Leukemia cancer (CML, AML, ALL and CLL) samples. Methods: Conventional cytogenetics: Peripheral Blood Culture (PBC) and bone marrow aspirate supplemented with mitogen Phytohemagglutinin (PHA) metaphase chromosomes were harvested aft er 72 hours for chromosome analysis. Image acquisition and analysis was performed by using automated karyotyping (IKAROS) soft ware based on GTG banding. Results: Philadelphia chromosome involving the reciprocal translocation between the long arms of chromosomes 9 and 22 (46, XY, t (9; 22)) was observed in majority of Chronic Myeloid Leukemia (CML) patients of the present study. Also a high number of chromosomal structural aberrations were observed in Fanconi Anemia (FA) patient, a chromosomal instability syndrome predisposing to cancer. Conclusion: Conventional cytogenetics can be the method of choice in diagnosis of genetic conditions like CML but for other bone marrow cancers more studies with high sample numbers need to be carried out for determination of clear cut markers.